Investigating intra-tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single-cell RNA sequencing

IF 7.9 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Jingyuan Huo, Zhen Wang, Wenting Zhao, Miao Chen, Haoyang Li, Fengpu He, Xiao Tian, Yaqi Ma, Firyuza Husanova, Liang Ma, Yiming Ni, Hongda Ding, Weidong Li, Hongfei Xu
{"title":"Investigating intra-tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single-cell RNA sequencing","authors":"Jingyuan Huo,&nbsp;Zhen Wang,&nbsp;Wenting Zhao,&nbsp;Miao Chen,&nbsp;Haoyang Li,&nbsp;Fengpu He,&nbsp;Xiao Tian,&nbsp;Yaqi Ma,&nbsp;Firyuza Husanova,&nbsp;Liang Ma,&nbsp;Yiming Ni,&nbsp;Hongda Ding,&nbsp;Weidong Li,&nbsp;Hongfei Xu","doi":"10.1002/ctm2.70113","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Primary cardiac angiosarcoma (PCAS) is a rare and aggressive heart tumour with limited treatment options and a poor prognosis. Understanding cellular heterogeneity and tumour microenvironment (TME) is crucial for the development of effective therapies. Here, we investigated the intratumoural heterogeneity and TME diversity of PCAS using single-cell RNA sequencing (scRNA-seq).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We performed scRNA-seq analysis on tumour samples from four patients with PCAS, supplemented with multicolour immunohistochemistry for identification. We used scRNA-seq data from five normal cardiac tissue samples downloaded from public databases for comparative analyses. Bioinformatic analyses, including Cell Ranger, Seurat, Monocle2, hdWGCNA, SCENIC and NicheNet, were utilized to identify distinct cell populations, transcriptional patterns, and co-regulating gene modules.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Our analysis revealed significant intratumoural heterogeneity in PCAS driven by diverse biological processes such as protein synthesis, degradation, and RIG-I signalling inhibition. The SCENIC analysis identified three primary transcription factors' clusters (<i>CEBPB</i>, <i>MYC</i> and <i>TAL1</i>). T-cell subset analysis showed exhausted antigen-specific T-cells, complicating the efficacy of immune checkpoint blockade. Furthermore, we observed suppressive macrophages (SPP1+ and OLR1+) and reduced mitochondrial gene <i>MT-RNR2</i> (MTRNR2L12) expression in TME-infiltrating cells, indicating impaired mitochondrial function.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>This study elucidates the complex cellular landscape and immune microenvironment of PCAS, highlighting potential molecular targets for the development of novel therapies. These findings underscore the importance of a multifaceted therapeutic approach for addressing the challenges posed by PCAS's heterogeneity and immune evasion.</p>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>Insights into the heterogeneity and transcriptional patterns of sarcoma cells may explain the challenges in treating primary cardiac angiosarcoma (PCAS) using the current therapeutic modalities.</li>\n \n <li>Characterization of the immune microenvironment revealed significant immunosuppression mediated by specific myeloid cell populations (SPP1+ and OLR1+ macrophages).</li>\n \n <li>Identification of mitochondrial dysfunction in immune cells within the PCAS microenvironment, particularly the notable downregulation of the MTRNR2L12 protein, suggests a new avenue for therapeutic targeting.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 12","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631565/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70113","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Primary cardiac angiosarcoma (PCAS) is a rare and aggressive heart tumour with limited treatment options and a poor prognosis. Understanding cellular heterogeneity and tumour microenvironment (TME) is crucial for the development of effective therapies. Here, we investigated the intratumoural heterogeneity and TME diversity of PCAS using single-cell RNA sequencing (scRNA-seq).

Methods

We performed scRNA-seq analysis on tumour samples from four patients with PCAS, supplemented with multicolour immunohistochemistry for identification. We used scRNA-seq data from five normal cardiac tissue samples downloaded from public databases for comparative analyses. Bioinformatic analyses, including Cell Ranger, Seurat, Monocle2, hdWGCNA, SCENIC and NicheNet, were utilized to identify distinct cell populations, transcriptional patterns, and co-regulating gene modules.

Results

Our analysis revealed significant intratumoural heterogeneity in PCAS driven by diverse biological processes such as protein synthesis, degradation, and RIG-I signalling inhibition. The SCENIC analysis identified three primary transcription factors' clusters (CEBPB, MYC and TAL1). T-cell subset analysis showed exhausted antigen-specific T-cells, complicating the efficacy of immune checkpoint blockade. Furthermore, we observed suppressive macrophages (SPP1+ and OLR1+) and reduced mitochondrial gene MT-RNR2 (MTRNR2L12) expression in TME-infiltrating cells, indicating impaired mitochondrial function.

Conclusion

This study elucidates the complex cellular landscape and immune microenvironment of PCAS, highlighting potential molecular targets for the development of novel therapies. These findings underscore the importance of a multifaceted therapeutic approach for addressing the challenges posed by PCAS's heterogeneity and immune evasion.

Key points

  • Insights into the heterogeneity and transcriptional patterns of sarcoma cells may explain the challenges in treating primary cardiac angiosarcoma (PCAS) using the current therapeutic modalities.
  • Characterization of the immune microenvironment revealed significant immunosuppression mediated by specific myeloid cell populations (SPP1+ and OLR1+ macrophages).
  • Identification of mitochondrial dysfunction in immune cells within the PCAS microenvironment, particularly the notable downregulation of the MTRNR2L12 protein, suggests a new avenue for therapeutic targeting.

Abstract Image

求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
15.90
自引率
1.90%
发文量
450
审稿时长
4 weeks
期刊介绍: Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信